The present invention provides novel 5-substituted pyrazolo[4,3-d]pyrimidine-7-one compounds. The structurally novel class of compounds contain a ring system numbered clockwise starting with the nitrogen in the diazole substitutent nearest the pyrimidinone ring fused thereto as shown by Formula XL. ##STR1## In particular, this invention relates to a combination of substituents on the ring system XL in the one, three, and five position not hitherto known referred to above as 5-substituted pyrazolo[4,3-d]pyrimidine-7-one compounds.
The present invention also relates to novel methods for the synthesis and use of the novel 5-substituted pyrazolo[4,3-d]pyrimidine-7-one compounds disclosed herein. The disclosure particularly relates to the novel compounds for use in the treatment of caridovascular disorders, such as heart failure, or cardiac insufficiency. The novel compounds are found to bind to an adenosine receptor and thus function as antagonists to adenosine or adenosine receptor agonists. Of special interest is the selective inhibition of phosphodiesterase by the novel compounds of the present invention.
Various references disclose compounds having the pyrazolo[4,3-d]pyrimidine-7-one ring system shown by Formula XL. For Example, 1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-7-(6H)-ones useful as anticonvulsants, sedatives, and antiinflammatory and gastric antisecretory agents are disclosed in U.S. Pat. No. 3,939,161 assigned to Abbott Laboratories. However, the disclosed pyrazolo[4,3-d]pyrimidine-7-(6H)-one is limited at the five position on the ring to hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, morpholinomethyl, piperidinomethyl, methoxymethyl, N-methylpiperazinomethyl, benzylthiomethyl, carbethoxy or p-chlorophenoxymethyl.
In Liebigs. Ann. Chem., 7131, 149 (1968) a synthesis of 1-phenyl-5-substituted pyrazolo[4,3-d]pyrimidine-7-ones is taught where the substituent at the five position is methyl, phenyl, benzyl, paramethylbenzyl, naphthyl, cyanoalkyl, or ethoxyethyl. The synthesis does not include any compounds which do not require a phenyl group in the one position. Further, no utility is taught.
Of less interest are compounds having the 3,4-d ring system and shown by the Formula XX ##STR2## as disclosed in Synthesis, p. 727 (1981) and shown by the Formula XXX ##STR3## as disclosed in Bull. Chem. Soc. Japan, 52(1), 208 (1979).
None of the compounds as disclosed and discussed above teach the novel compounds of the present invention having the present combination of substituents on the ring system of Formula XL.